The story of living in spite of melanoma, metastasis, vaccines, anti-PD-1, lung removal, and stereotactic radiation. The story of life with family and friends. {Posts under ~ Sew Chaotically, Travel Chaotically, and Chaotic Cookery also housed within! A girl's gotta have fun!}

About Me

Who am I? That is a question the rest of you could probably answer better than I. I am a wife, mother, daughter, sister, friend, pediatric nurse practitioner, cook, teacher, gardener, lover of words and music, occasional seamstress, and homemaker. I do have a couple of talents of questionable merit: I can create a decent meal in less than 30 minutes. I can feed and/or soothe almost any baby. And I can remember practically any song I've ever heard. For the rest, I'd rather those who know me decide.

Once melanomas have
progressed with acquired resistance to mitogen-activated protein kinase
(MAPK)-targeted therapy, mutational heterogeneity presents a major challenge.
We therefore examined the therapy phase before acquired resistance had
developed and discovered the melanoma survival oncogene MITF as a driver of an
early non-mutational and reversible drug-tolerance state, which is induced by
PAX3-mediated upregulation of MITF. A drug-repositioning screen identified the
HIV1-protease inhibitor nelfinavir as potent suppressor of PAX3 and MITF
expression. Nelfinavir profoundly sensitizes BRAF and NRAS mutant melanoma
cells to MAPK-pathway inhibitors. Moreover, nelfinavir is effective in
BRAF and NRAS mutant melanoma cells isolated from patients progressed on MAPK inhibitor
(MAPKi) therapy and in BRAF/NRAS/PTEN mutant tumors. We demonstrate that
inhibiting a driver of MAPKi-induced drug tolerance could improve current
approaches of targeted melanoma therapy.